Avian leukosis virus infections produce a variety of tumors which are especially useful model systems. Extensive studies into the molecular biology of tumor viruses are revealing the genes which cause neoplastic transformation. This creates a single system in which our understanding of cancer can extend from nucleic acid sequence of oncogenes through tumor formation, to tumor immunobiology. Macrophages are essential accessory cells in T lymphocyte-dependent responses as well as control of the stem cell differentiation. Chicks infected with an osteopetrosis inducing avian leukosis virus develop the abnormal bone growth. They also show an inhibition of blastogenic response to the T lymphocyte-dependent lectin concanavalin A by spleen and thymus cells, although blood cell cultures react normally. The defect is in the macrophage, T cells are capable of responding. The purpose of the project is to discover the type of cellular defect of the macrophage accessory cell. One of two mechanisms is expected: failure to produce the needed soluble factor or failure to present the stimulatory ligand to potentially responsive T cells. This will be done by testing adherent cell populations of normal and diseased chicks for their activity in appropriate macrophage dependent response systems. Since stimulus-pulsed T cells can respond after nonpulsed macrophages are added, this is a test for soluble factor. Similarly, MLR are macrophage dependent, but because the macrophage can be replaced by soluble factor, they need not present the antigen. Supernatants from activated macrophages and Con A-stimulated spleen cells will be used to reconstitute the response of cells from diseased chicks. These studies will be done evaluating endotoxin effects, since endotoxin stimulates activated macrophage to become tumoricidal. This investigation will supply much information about key questions of macrophage heterogeneity and development, and about their effects on the development and activity of other cells in the marrow from stem cells. This is important in tumor immunology and viral oncology, as well as for understanding the faulty control of bone tumor cells.